title: Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein.
abstract: Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. weiser@mail.med.upenn.edu
authors.forename: J N
authors.initials: JN
authors.lastname: Weiser
authors.forename: N
authors.initials: N
authors.lastname: Pan
authors.forename: K L
authors.initials: KL
authors.lastname: McGowan
authors.forename: D
authors.initials: D
authors.lastname: Musher
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001770:Blood Bactericidal Activity / Q000276:immunology*; D002097:C-Reactive Protein / Q000276:immunology*; D018604:Epitope Mapping; D005838:Genotype; D006192:Haemophilus Infections / Q000276:immunology* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D012137:Respiratory System / Q000276:immunology* / Q000382:microbiology
chemical_list: D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D010767:Phosphorylcholine; D002097:C-Reactive Protein